Maintaining consistent quality and clinical performance of biopharmaceuticals

ABSTRACT

Introduction: Biopharmaceuticals are large protein based drugs which are heterogeneous by nature due to post translational modifications resulting from cellular production, processing and storage. Changes in the abundance of different variants over time are inherent to biopharmaceuticals due to their sensitivity to subtle process differences and the necessity for regular manufacturing changes. Product variability must thus be carefully controlled to ensure that it does not result in changes in safety or efficacy.

Areas covered: The focus of this manuscript is to provide improved understanding of the science and strategies used to maintain the quality and clinical performance of biopharmaceuticals, including biosimilars, throughout their lifecycle. This review summarizes rare historical instances where clinically relevant changes have occurred, defined here as clinical drift, and discusses modern tools used to prevent such changes, including improved analytics, quality systems and regulatory frameworks.

Expert opinion: Despite their size complexity and heterogeneity, modern analytics, manufacturing quality systems and comparability requirements for the evaluation of manufacturing changes cumulatively help to ensure the consistent quality and clinical performance of biopharmaceuticals throughout their product lifecycle. Physicians and patients can expect the same safety and efficacy from biopharmaceuticals and their respective biosimilars irrespective of batch or production history.

KEYWORDS:

• Biopharmaceutical
• biosimilar
• consistency
• drift
• equivalence
• manufacturing

Article highlights

• Biopharmaceutical heterogeneity and variability are inherent in this product class due to cell based production and the necessity for regular manufacturing process changes

• Biopharmaceutical variability resulting in clinical differences is extremely rare with only a single verifiable case resulting in adverse events in over 35 years and over 260 products

• Analytical capabilities and modern quality systems are continually evolving to ensure consistent biopharmaceutical quality. Recent improvements include: (i) Quality by design (ii) Continued process verification and (iii) Two tiered reference standards.

• Although the abundance of specifc variants may vary, the demonstration of comparability following manufacturing changes ensures equivalent clinical performance throughout the product lifecycle.

• Originator and biosimilar biopharmaceuticals employ identical quality systems and regulatory frameworks to maintain consistent quality and clinical performance.

• Physicians and patients can expect the same safety and efficacy from biopharmaceuticals and their respective biosimilars irrespective of batch or production history.

This box summarizes key points contained in the article.

Declaration of interest

The authors are employees and shareholders of Sandoz, a division of Novartis, which develops, manufactures and markets biopharmaceuticals, including biosimilar products. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Supplementary material

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Additional information

Funding

No funding to declare.